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Biomedical subjects

C Roth

Publications and source records attributed to C Roth.

At least 145 records · Page 8Linked to original sources
PubMed1990

Thymic carcinoma. Report of five cases and review of the literature.

Among 54 mediastinal tumours we examined in the past 20 years, there were 5 cases of primary thymic carcinomas, each with widespread metastases. Histological features in three cases were consistent with lymphoepithelioma-like carcinoma. One case showed an epidermoid pattern with keratotic pearls resembling Hassall bodies. One undifferentiated carcinoma developed from a cortical thymoma. Epstein-Barr virus could not be detected in tumour tissue with in situ hybridization. A review of the literature revealed only 94 well-documented cases of thymic carcinoma. Both thymic carcinomas and thymomas are neoplasms of the thymic epithelial cells, but thymic carcinomas are obviously histologically malignant and usually not associated with any parathymic syndromes. Epidermoid and lymphoepithelioma-like carcinomas are described along with special forms, such as small- and clear-cell carcinomas, basaloid, sarcomatoid, mucoepidermoid, and adenocystic carcinoma. Compared to the other forms, lymphoepithelioma-like carcinoma has a poor prognosis in regard to metastases and rate of survival. Some thymic carcinomas may develop from pre-existing thymomas.

Adult↗
PubMed1989

Active late-appearing variable surface antigen genes in Trypanosoma equiperdum are constructed entirely from pseudogenes.

The expression of genes coding for variable surface glycoproteins (VSGs) in Trypanosoma equiperdum is linked to duplicative transpositions of silent, basic copy sequences into telomere-linked expression sites. Examination of three independently derived late-appearing trypanosome clones expressing VSG-78 revealed that the expressed gene in all cases is composed of sequences derived from three or four individual silent genes. The 182 base pairs at the 3' end of the coding sequence are derived from one silent gene, the 3' donor. The remaining 5' segment is a mosaic structure containing variable-length segments derived from two, or perhaps three, related silent genes. All of the silent genes that participate in the construction of the VSG-78 expression-linked copy (ELC) genes contain multiple stop codons and are unable to code for VSGs. Individual silent pseudogenes complement one another in the mosaic structure of the 5' portions of the ELC genes and create functional VSG genes. The joining of the 3' and 5' portions of the composite genes occurs in short regions of homology and suggests a mechanism by which the ordered expression of the VSG genes is generated.

Animals↗
PubMed1988

Allogeneic manipulation of the GAT idiotypic cascade. Immunization of C57BL/6 mice by BALB/c anti-idiotypes stimulates similar strain-specific V genes as the original antigen.

Antibodies specific for the immunizing Ag (Ab1) (Id+ Ag+) and Ab3 (Id+ Ag+ or Id+ Ag-) of the (Glu60 Tyr10 Ala30) (GAT) idiotypic cascade express similar pGAT public determinants in BALB/c and C57BL/6 strains. These determinants have been shown to be dependent upon both VH and Vkappa encoded segments. The VH of the BALB/c Ab1 (germ-line gene H10) and that of the C57BL/6 Ab1 (germ-line gene V186-2) are only 75% homologous, whereas VK are much more conserved. C57BL/6 mice were immunized with BALB/c Ab2 (anti-idiotypic) antibodies and monoclonal Ab3 were derived after fusion of immunized spleen cells with the nonsecreting hybridoma cell line Sp/2.0-Ag. From 13 cell lines, five clones (four Id+ Ag- and one Id+ Ag+) were isolated and the mRNA V regions sequenced. Immunization with BALB/c anti-idiotypes elicits expression of the same or closely related C57BL/6 VH and Vkappa genes as when C57BL/6 mice were immunized with GAT, although functional VH BALB/c equivalents have been isolated in the B6 strain. Our results suggest that manipulation of the repertoire via antigenic or idiotypic stimulation both lead to the expression of different genes in different strains. They further confirm that the immune system is largely degenerate, for both idiotype expression and Ag recognition.

Amino Acid Sequence↗
PubMed1988

Biochemical characterization and biological effects of partially purified B cell-activating factor (BCAF).

B cell-activating factor (BCAF) has been characterized and partially purified from the supernatant of the murine tumor T cell line 373. BCAF has an apparent molecular mass of 15 to 20 kDa when analyzed by Superose 12 fast protein liquid chromatography (FPLC) gel filtration and a pI of 4.5 to 5.0 when analyzed by FPLC chromatofocusing. Concentrated supernatant was applied to a nickel chelating column and unadsorbed active material was further purified by two sequential C4 reverse-phase high-performance liquid chromatography steps. This purification procedure allowed a complete separation of interleukin 2 and interleukin 4 activities from BCAF. This partially purified BCAF induces Ia expression, cell size increase and proliferation of small resting B cells. Furthermore, we have shown that the activity of partially purified BCAF is insensitive to treatment by monoclonal antibodies specific for interleukin 4 and interleukin 5.

Animals↗
PubMed1988

IL-4, but not IL-5, can act synergistically with B cell activating factor (BCAF) to induce proliferation of resting B cells.

B cell activating factor (BCAF) was initially identified in the supernatant of the murine T helper cell clone 52-3 (52-3 SN) because of its ability to promote activation and proliferation of resting B cells in the absence of any other costimulus. In this paper, we show that 52-3 T helper cells also secrete IL-4 and IL-5 and we have analyzed the influence of these two lymphokines on B cell proliferation induced by BCAF-containing 52-3 SN. Using the neutralizing anti-IL-4 monoclonal antibody 11B11, we observed partial inhibition of B cell proliferation. 52-3 SN free of IL-4 prepared using an immunoabsorbent column was still able to induce significant B cell proliferation. Although recombinant IL-4 alone does not induce B cell proliferation, it increased the proliferation induced by IL-4-free 52-3 SN. Kinetic studies showed that IL-4 is required at the start of B cell cultures in order to exert optimal synergistic effects. In contrast, anti-IL-5 monoclonal antibody NC17 did not affect the B cell proliferative activity of 52-3 SN whether or not IL-4 was present. When 52-3 SN was tested on dextran-sulfate-activated B cells, IL-5 and BCAF activities were detected but only the IL-5 activity was neutralized by monoclonal antibody NC17. These results demonstrate that (i) BCAF-containing SN can induce proliferation of resting B cells independently of IL-4 and IL-5, and (ii) IL-4, but not IL-5, can act synergistically with BCAF to induce B cell proliferation.

Animals↗
PubMed1987

Antigenic variation in parasitic protozoa.

Antigenic variation in the protozoan parasites responsible for malaria and African sleeping sickness is examined. Some of the molecular mechanisms responsible for the generation of new variant antigens are reviewed and the possible problems posed by this process in the development of vaccines against these parasites are discussed.

Animals↗
PubMed1986

Bone block transfer of coracoacromial ligament in acromioclavicular injury.

A bone block transfer of coracoacromial ligament into the medullary canal of the clavicle for Grade III acromioclavicular injury was developed in an attempt to prevent occasional pullout of the ligament in the procedure described by Weaver and Dunn. Fifteen consecutive cases (12 acute, three chronic) with Grade III acromioclavicular injury were treated by this method. All but one patient regained painless full range of shoulder motion. All patients returned to previous activity. Failure of coracoclavicular reconstruction occurred in one case. Asymptomatic focal myositis ossificans developed in four cases with no functional deficit.

Acromioclavicular Joint↗
PubMed1985

Immune response against poly(Glu60,Ala30,Tyr10) (GAT): immunization with monoclonal anti-idiotypic antibodies leads to the predominant stimulation of idiotypically similar immunoglobulins with anti-GAT activity.

Two monoclonal anti-idiotypic antibodies (HP-Id20 and HP-Id22) recognizing two different public idiotopes expressed in the anti-poly(Glu60,Ala30,Tyr10) (GAT) response were used to immunize BALB/c and C57BL/6 mice. From these animals hybridomas were isolated. From BALB/c and C57BL/6 mice eight and seven monoclonal antibodies were characterized, respectively. The reagents were classified according to the expression of the public idiotypic specificity p.GAT (recognized by a rabbit antiserum). The anti-GAT activity and the expression of the various idiotopes characterized on anti-GAT polyclonal and monoclonal antibodies were also studied. Most of the reagents are Ab1'-type of antibody resembling anti-GAT antibodies. One anti-anti-idiotypic monoclonal antibody (Ab3) was also isolated from BALB/c mice. This suggests that in this experimental model the repertoire induced after HP-Id immunization and antigen stimulation is comparable. The idiotypic analysis of a large number of anti-GAT and of Ab1' monoclonal antibodies suggests that only two public idiotopes are involved in the anti-GAT response.

Animals↗
PubMed1985

Characterization of monoclonal antibodies against prostaglandin E2: fine specificity and neutralization of biological effects.

The specificity and heterogeneity of the immune response of BALB/c mice immunized with prostaglandin E2 (PGE2) coupled to thyroglobulin was studied. All the animals (n = 50) responded to PGB2, a transformation product of PGE2. However, following repeated injections most of the animals (n = 30) were also able to respond to PGE2. Cellular hybridizations were performed and five anti-PGE2 monoclonal antibodies were isolated and analysed. They are mainly directed against the ring and the omega-chain of PGE2 but their specificity toward the alpha-chain is more limited. The association constants are greater than to 1 X 10(9) M-1. The monoclonal antibody 8E.57.71 (Ka = 1.3 X 10(10) M-1) is particularly convenient for sensitive radioimmunoassays (detection limit 25pg/ml, when iodinated tracer is used). Anti-PGE2 monoclonal antibodies were found to neutralize the specific binding of [3H]PGE2 to rat brain hypothalamic receptors and to inhibit the PGE2 induction of rat fundus muscular contraction.

Animals↗
PubMed1985

Gene repertoire of the anti-poly(Glu60Ala30Tyr10) (GAT) immune response: comparison of VH, V kappa, and D regions used by anti-GAT antibodies and monoclonal antibodies produced after anti-idiotypic immunization.

Eight monoclonal antibodies were selected from BALB/c mice immunized with two different monoclonal anti-idiotypic antibodies recognizing two discrete idiotopes characteristic of the anti-poly(Glu60Ala30Tyr10) (GAT) antibody response. These monoclonal antibodies were previously classified as Ab1 (anti-GAT-like) and Ab3 (anti-anti-idiotype) on the basis of expression of the public idiotypic specificity (p.GAT) studied with a xenogeneic serum, anti-GAT activity, and expression of various public idiotopes. All the heavy chain variable region (VH) sequences from Ab1 are nearly identical to the VH sequences of Ab1 anti-GAT monoclonal antibodies. The same type of results has been found with the Ab1 kappa light chain variable region (V kappa) sequences. Confirming our classification, Ab3 VH and V kappa sequences were found to be completely different from Ab1 VH and V kappa sequences. The Ab1 diversity (D) regions are different from one another and different from the D regions found on monoclonal anti-GAT antibodies but function similarly. These D regions are not simply derived from already described D genes. Finally, our results suggest that in the anti-GAT response VH and V kappa sequence are mainly responsible for idiotype expression.

Amino Acid Sequence↗
PubMed1985

Scintigraphic dissociation of reticuloendothelial and hepatocyte function in chronic vitamin A hepatotoxicity.

A discordant hepatic uptake between Tc-99m sulfur colloid and Ga-67 citrate has occurred in an adult patient with hepatotoxicity due to hypervitaminosis A. The authors believe this is a scintigraphic phenomenon related to the characteristics of the radiopharmaceuticals used and does not necessarily represent a true dissociation of various cellular functions of the liver.

Chemical and Drug Induced Liver Injury↗
PubMed1985

Induction by monoclonal anti-idiotypic antibodies of an anti-poly(Glu60 Ala30 Tyr10) (GAT) immune response in GAT-responder and GAT-nonresponder mice.

Two different monoclonal anti-idiotypic (Id) antibodies, HP-Id20 and HP-Id22, recognizing two discrete idiotopes characteristic of the anti-poly(Glu60 Ala30 Tyr10) (GAT) response were used to immunize BALB/c (GAT-responder) and DBA/1 (GAT-nonresponder) mice. The monoclonals were injected either copolymerized with keyhole limpet haemocyanin or polymerized with glutaraldehyde. The specific response was studied by two assays: (a) inhibition of binding of monoclonal anti-GAT antibody G5Bb2-2 to HP-Id20 and HP-Id22 and (b) GAT binding assays. In BALB/c GAT-responder mice, HP-Id20 and HP-Id22 immunization led to the preferential stimulation of immunoglobulin idiotypically related to anti-GAT antibodies (Ab1') and expressing anti-GAT activity. The results obtained with BALB/c nu/nu mice indicated that this response is T-cell-dependent. By means of the same experimental protocol GAT-nonresponder animals could be induced to produce anti-GAT antibodies after HP-Id immunization. This last result indicates that anti-Id immunization can bypass Ir gene control and does not preferentially stimulate the induction of GAT-specific T suppressor cells.

Animals↗
PubMed1984

Poly(Glu60,Ala30,Tyr10) (GAT)-specific T cells do not express B cell public idiotopes but can be primed by monoclonal anti-idiotypic antibodies.

Eight monoclonal anti-idiotypic antibodies directed against public idiotopes have been further characterized: (a) they bind to public idiotopes with a high affinity; (b) they recognize all anti-poly(Glu60,Ala30,Tyr10) (GAT) antibodies as measured by inhibition of the anti-GAT plaque-forming cell response. This has been verified in three strains of mice. These reagents were not able to detect idiotope expression on eight GAT-specific helper T cell lines and clones. This result was obtained by two techniques: (a) idiotope expression at the T cell surface was measured by indirect immunofluorescence using a cell sorter with surface antigens H-2D, Thy-1.2, Lyt-1 and L3T4 as positive controls; (b) after immunoadsorption of [35S] methionine-labeled cellular extracts from two lines, no unique molecule was retained by the HP-idp22 monoclonal anti-idiotypic antibody coupled to Sepharose. Despite these negative results, this antibody was found to prime lymph node cells in vivo, which were able to proliferate specifically in response to GAT. Two T cell lines derived from this lymphocyte population do not express any of the idiotopes tested. These results suggest that monoclonal anti-idiotypic antibodies may be influencing T lymphocyte activity indirectly.

Animals↗
PubMed1984

Cholera toxin treatment stimulates tumorigenicity of Rous sarcoma virus-transformed cells.

Chinese hamster ovary cells transformed by Rous sarcoma virus form tumors poorly in nude mice. Tumorigenicity was markedly stimulated by pretreatment of the cells with cholera toxin, which raises cyclic AMP levels and activates cyclic AMP-dependent protein kinase. Increased tumorigenicity was manifested by a severalfold increase in the rate of tumor formation, as well as earlier appearance and more rapid growth of tumors. In contrast, spontaneously transformed Chinese hamster ovary cells showed decreased tumorigenicity after cholera toxin treatment. The activation of tumorigenic potential in Rous sarcoma virus-transformed Chinese hamster ovary cells by cholera toxin correlated with increased phosphorylation of the viral oncogene product pp60src and stimulation of its tyrosine kinase activity.

Animals↗
PubMed1984

The use of monoclonal anti-idiotypic antibodies for studying antigen-specific T and B cell receptors.

Eight syngeneic HP-id specific for anti-GAT antibodies are tested for their capacity to detect idiotypes on GAT-specific T cell lines. Their affinity constants are between 5 X 10(-7) and 10(-8) molar-1 which permit significant binding analysis. They detect idiotopes expressed in anti-GAT sera from all the strains of mice tested and by 14 BALB/c HP-GAT. In addition, the distribution of the corresponding idiotopes among all allogeneic HP-GAT allow the identification of two groups of idiotopes. Some idiotopes are expressed by a minority of HP-GAT; the other idiotopes are expressed by all of them. Nevertheless, in spite of the broad molecular and genetic distribution of these idiotopes on anti-GAT antibodies, they are not expressed by three GAT-specific T cell lines from different genetic origins.

Animals↗